A major challenge for the subunit vaccine approach to AIDS is the induction of broadly cross-reactive neutralizing antibodies. Recent human trials with recombinant glycoprotein 120 vaccines indicate that many as yet undefined problems lie ahead. On the other hand, a few conformationally sensitive monoclonal antibodies have been identified including those cloned from infected individuals demonstrating that a natural origin for potent, broadly cross-reactive neutralizing responses in humans exists. Our proposal is directed to the identification of synthetic peptide mimetics corresponding to epitopes defined by these antibodies. for this work, we will rely on new procedures developed in our laboratory for folding peptides with covalent hydrogen bond.mimics. A strong structural group at TSRI will collaborate on this project for structure prediction, and X-ray crystallography. Mimetics will be incorporated into MAPS with "universal" T-cell epitopes and their immunogenicity evaluated in animals. HIV-I neutralization assays will be carried out by our collaborators.